Biological Innovation and Active Genetics

How the amazing diversity of body shape and structures arises is a long-standing, unsolved problem in evolutionary biology.  As an Allen Distinguished Investigator, Ethan Bier will lead a team exploring the molecular genetic basis of biological innovation itself.

Our understanding of evolution is largely based on identifying individual genes or regulatory elements that have contributed substantially to evolutionary innovations. Changes in a relatively small number of these genetic elements are responsible for many large-scale changes we observe in animals.

We still know very little about the genetic programs responsible for larger leaps in species transformations over evolutionary distances of millions of years. How many and what types of changes would transform an arm or a wing? What principles govern design modifications in nature? Access to this knowledge would unlock the potential to build organs or organisms that embody useful innovations, such as improving carbon dioxide fixation in land plants to enhance their yield, and to understand how cancers evolve rapidly to evade drug therapies. The team will explore how changes in regulatory genes can accomplish dramatic transformations in the sizes and shapes of species, while maintaining viability and fertility.

Making these kinds of genetic changes requires increasing the size and speed with which genome segments can be replaced—a technology the team calls “active genetics.” These methods, built on Crispr-Cas9 technology and a new method for generating insertional mutations called the Mutagenic Chain Reaction, will seamlessly replace large DNA segments while overcoming limits of Mendelian genetics.

This work has the potential to unlock the design principles of evolution. The practical applications of being able to dramatically alter complex traits like body size, wing shape, and fruit size through principle-based biological innovation would generate powerful tools to be employed in biology, medicine, agriculture and environmental sciences.

Affiliated Investigators

Ethan Bier, Ph.D.

University of California, San Diego

Ethan Bier is a professor in the section of Cell and Developmental Biology at UC San Diego.  During the past 25 years at UCSD Dr. Bier has studied how secreted morphogen proteins subdivide the dorsal-ventral axis of the fruit fly embryo into neural versus epidermal regions and how such processes result in the formation of sharp boundaries during development of the wing. These are among the most conserved evolutionary processes.

Dr. Bier has also used fruit flies to study mechanisms of human disease, focusing on understanding the mechanisms by which bacterial toxins contribute to breaching host barriers. Thus, two toxins produced by anthrax bacteria trigger potentially fatal vascular leakage while cholera toxin leads to breakdown of the intestinal barrier leading to acute life-threatening diarrhea. His findings that these toxins disrupt transport of proteins to cell junctions required for barrier integrity suggest possible therapeutic approaches to combat anthrax and cholera as well as a variety of inflammatory diseases such as IBD and asthma, which also involve barrier dysfunction. Dr. Bier recently has made a discovery allows the conversion of heterozygous mutants to homozygotes that promises to revolutionize control of vector borne diseases (e.g., malaria) and pests, genetic manipulation of organisms for medical and agricultural research, and treatment of cancer, HIV, and other maladies.

Dr. Bier graduated Phi Beta Kappa as a Regents Scholar from UCSD in 1978 with degrees in Biology and Mathematics. He received his Ph.D. from Harvard Medical School on regulation of immune genes in Dr. Allan Maxam’s laboratory from 1978-1985. He did his postdoctoral studies on development of the nervous system at UCSD with Drs. Lily and Yuh Nung Jan (1985-90) and then assumed a faculty position at UCSD in 1990. He is an Alfred P. Sloan and Basil O’Connor Scholar.